Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

ObjectiveTo clarify the accumulation and distribution characteristics of dry matter and mineral elements in Artemisia argyi var. argyi cv. Qiai， and to provide technical support for the high yield of and efficient utilization of nutrients in this medicinal species. MethodTwo cultivars of this species， Qiqing 1 and Qihuang 1 were selected， and the composition of dry matter in different organs， the content， accumulation， and distribution of mineral elements in each organ of the two cultivars， and the dynamic changes of volatile oil content and index components eucalyptol and borneol in leaves of the two cultivars were monitored at different growth stages. ResultThe period from February to March marked the early growth stage of Qiai， and the dry matter was mainly distributed in the leaves. It accelerated the growth in April， and the period from April to mid-June witnessed the vigorous vegetative growth of Qiai， during which the dry matter was mainly found in the stems and leaves. It began the reproductive growth from late June and the dry matter was mainly distributed in the stems. In the flowering stage in August， no dry matter accumulation occurred. As for the volatile oil， the content was high （> 1.10%） at the vigorous vegetative growth stage and peaked on June 14 （1.33% in Qiqing 1， and 1.23% in Qihuang 1）. The relative mass fraction of eucalyptol was the maximum at the vegetative growth stage （8.67% in Qiqing 1， and 13.07% in Qihuang 1）. The relative mass fraction of borneol peaked at the early growth stage （2.63% in Qiqing 1， and 5.94% in Qihuang 1）. The content of nitrogen， phosphorus， potassium， and zinc in leaves was in significantly positive correlation with the content of volatile oil and the relative content of eucalyptol and borneol. The content of macroelements nitrogen， phosphorus， potassium， and calcium and trace elements iron and zinc peaked at the early growth stage， and the content was the highest in stem and leaf. The content of macroelement magnesium and trace elements manganese and copper was the highest at vegetative growth stage when the content of other elements decreased and the nutrients were gradually transferred to the buds， flowers and other organs. In the whole growth period， the distribution of potassium， calcium， and zinc was in the order of leaf > stem > root， and the distribution of nitrogen， phosphorus， copper， magnesium， and manganese followed the order of leaf > root > stem. The distribution of iron was in the order of root > leaf > stem. There was a significantly positive correlation between the total amount of dry matter and the absorption of nutrients in 'Qiai'. The absorption of macroelements by Qiai was in the order of potassium > nitrogen > calcium > phosphorus > magnesium， and the ratio of absorbed elements was about 2.66∶2.51∶0.6∶0.11∶0.04. The absorption of trace elements followed the order of manganese > iron > zinc > copper， and the ratio of absorbed elements was about 0.25∶0.17∶0.05∶0.04. In terms of the production of medicinal materials， 'Qiai' needed about 4.11 kg potassium， 3.58 kg nitrogen， 0.91 kg phosphorus， 0.18 kg calcium， 0.06 kg magnesium， about 6.64 g manganese， 2.56 g iron， 1.30 g zinc， and 0.92 g copper to produce 100 kg medicinal materials. ConclusionEnough organic fertilizer and phosphorus and potassium fertilizers should be applied as base fertilizers for Qiai. The vegetative growth stage （April-June） marks the high accumulation of dry matter and large demand of nutrients， during which topdressing should be conducted timely and early， especially nitrogen fertilizer， and appropriate amount of micro-element fertilizer should be added. Qiai needs a large amount of calcium and magnesium fertilizers from the mid-vegetative growth stage， and they should be applied in time in the late stage to ensure the vegetative growth of the plants for seeds and the quality of the medicinal material of Qiai.

With the development of computer and digital technology, the application of computer-aided technology has become a new trend in the field of oral implant. Computer-guided oral implant surgery has the advantages of being safer and more accurate than traditional implant surgery, and it can truly realize the concept of restoration-oriented implant. However, computer-guided oral implant surgery has various steps which cause deviations accumulation, so that some clinicians remain sceptical about the accuracy of the technology. Currently, due to the lack of a quantitative system for evaluating the accuracy of computer-guided oral implantation, the implant deviation in each step is still inconclusively in the stage of research and debate. The purpose of this paper is to summarize the advantages and disadvantages, research progress, accuracy and influencing factors of computer-guided oral implantation, aiming to provide a reference for improving implant accuracy and guiding clinical design and surgery.
Computer-Aided Design ; Computers ; Cone-Beam Computed Tomography ; Dental Implants ; Imaging, Three-Dimensional ; Patient Care Planning ; Surgery, Computer-Assisted

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
Humans ; Lung Neoplasms/drug therapy* ; Treatment Outcome ; Neoplasm Recurrence, Local/chemically induced* ; Quinolines/adverse effects*

Animals ; CRISPR-Cas Systems ; Gene Editing ; Humans

Non-small cell lung cancer (NSCLC) is one of the malignant diseases with high morbidity, high mortality and poor prognosis in China and worldwide, and the progression of which is significantly related to abnormal angiogenesis. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), inhibits angiogenesis during tumor progression. It has been widely demonstrated to improve the survival of NSCLC patients. Therefore, bevacizumab is approved and recommended as the first-line treatment of advanced NSCLC by a number of countries and regions. In this paper, various large-scale clinical trials are analyzed to highlight the current clinical applications of bevacizumab in advanced NSCLC, especially patients with EGFR mutations. In addition, this review focuses on the efficacy, safety and predict factors of bevacizumab as anti-angiogenic therapy, in order to screen the patients who can acquire the maximal benefit.

Objective: To establish and optimize the HPLC fingerprints of Angelica sinensis medicinal material and determine the ligustilide content to improve the quality standard for Angelica sinensis and improve the quality control level of Chinese angelica medici-nal material and preparations. Methods: A method for the determination of ligustilide was optimized by HPLC. The column was eluted on an Agilent ZORBAX SB C18(250 mm×4. 6 mm, 5 μm) column with acetonitrile-water (60 ∶ 40) as the mobile phase. The flow rate was 1. 0 ml·min-1, the detection wavelength was 326 nm, and the column temperature was at 35 ℃. The HPLC fingerprints of 13 batches of Angelica sinensis from different origins and methodological investigations were established and validated to set up an HPLC fingerprinting evaluation method for Angelica sinensis. Acetonitrile-0. 1% formic acid was used as the mobile phase with gradient elu-tion. The flow rate was 1. 0 ml·min-1, the detection wavelength was 280nm, and the column temperature was at 25℃. Results: The results showed that under the above HPLC conditions, ligustilide had good linearity within the range of 0. 032 3-0. 645 5 mg·ml-1(r=0. 999 9), and the average recovery was 100. 5% (RSD=1. 61% ,n=6). The quality fraction of ligustilide in Angelica sinensis was 0. 885 6%-2. 382 2% . Through the establishment of HPLC fingerprints of Angelica sinensis, the characteristic profiles with better peak shape and degree of separation and 18 common peaks with better resolution were obtained. The similarities of the 13 batches of angelica were all between 0. 9 and 1. 0. Conclusion: According to the methodological investigation, the HPLC fingerprints and ligustilide con-tent determination method of Angelica sinensis are simple, reliable, stable and feasible.

Objective To investigate the incidence and risk factors of deep venous thrombosis (DVT) of lower extremity in patients with pelvic or acetabular fracture.Methods From August 2015 to December 2016,110 patients with pelvic or acetabular fracture were treated in our hospital.They were 76 males and 34 females with a mean age of 44.2 years (range,from 16 to 76 years).There were 48 pelvic fractures,including 12 anterior and posterior compression,16 lateral compression and 20 vertical shear ones by the Young-Burgess classification;there were 62 acetabular fractures,including 26 simple and 36 complex ones by the Letournel-Judet classification.The incidence of lower extremity DVT was detected preoperatively and postoperatively using ultrasound detection.The factors associated with the incidence of DVT were analyzed statistically.The risk factors were screened by single factor logistic regression analysis;the major independe risk factors were determined by multi-factor logistic regression analysis.P ＜ 0.05 was considered as statistically significant.Results DVT occurred in 32 patients (29.09％),including 21 cases (19.09％) of proximal thrombosis and 3 cases of combined pulmonary embolism.The incidence of DVT in patients with acetabular fracture was significantly higher than in those with pelvic fracture (P ＜ 0.05);the incidence of proximal DVT in patients with complex acetabular fracture was significantly higher than in those with simple acetabular fracture (P ＜ 0.05).Multivariate analysis showed that age of ＞ 60 years,combined injuries and interval of ＞ 2 weeks from injury to surgery were independent risk factors for incidence of DVT (P ＜ 0.05).Conclusions The risk of lower extremity DVT is high in patients with pelvic or acetabular fracture in spite of active prophylaxis,especially the risk of proximal thrombosis.Age of ＞ 60 years,combined injuries and interval of ＞ 2 weeks from injury to surgery may be the independent risk factors for incidence of DVT.

Objective: To analyze the clinical, pathological and radiological characteristics of paragonimiasis in children for accurate diagnosis and therapy. Methods: A total of 31 patients with paragonimiasis treated from 2002 to 2016 were selected, including 17 cases from migrant areas and 14 cases from Wenzhou area. Results: In migrant children group, the serum IgE was significantly higher than that in Wenzhou area group [(2 379±944) IU/mL∶(1 552±1 121) IU/mL, t=-2.23, P<0.05], and the duration of therapy was remarkable longer [(13.8±6.5) days∶(9.9±3.4) days, t=-2.15, P<0.05]. Among all cases, 10 showed polyserositis including pleural effusion, ascites and pericardial effusion at different degrees on chest CT scans. Five cases with cerebral paragonimiasis were confirmed by MR imaging. Most of the lesions were located in the parietal lobe with slight low signal on T1WI but high signal on T2WI surrounded by disproportionate edema. Annular enhancement was prominent by Gd-DTPA. Paragonimiasis serum antibody was positive in all cases by ELISA. Pathologic features included formation of irregular lacunae or sinus tracts, presence of paragonimus bodies, and eosinophilic infiltration in the adjacent tissues. Conclusions Clinical manifestations of paragonimiasis are complex and non-specific in children.In migrant children group, clinical manifestations are diverse, more serious with more complications and difficulties in treatment, while patients in Wenzhou area group have favorable prognosis and less complicated treatment. The early diagnosis and timely treatment should be determined by patient′s detailed history, eosinophilic count, radiologic findings and immunological test to avoid serious complications.

Bronchoscopy is a minimally invasive method for obtaining peripheral pulmonary lesions (PPL). Traditional bronchoscopy-guided transbronchial lung biopsy (TBLB) is performed under X-ray guidance, and diagnostic rate is relatively low. A new, real-time electromagnetic navigation bronchoscopy (ENB) is a minimally invasive diagnostic technique which appeared in recent years. Studies suggest ENB is a feasible and safe method for diagnosis of PPL which shows higher diagnostic yields than traditional TBLB, and its potential application in localization and treatment of PPL. This article reviews the clinical application of the technique.